Perinatal HIV-1 transmission, the route by which most children are now infected, is expected to increase as growing numbers of women of reproductive age become infected. Our current prospective study and others indicate that about one-third of infants born to seropositive women will be infected. This proposal addresses several critical issues related to perinatal HIV-1 transmission: maternal factors associated with perinatal transmission, assays for early detection of infection in infants, and the long term outcome of perinatal infection with particular emphasis on the neurodevelopmental outcome. Three populations will be enrolled for prospective longitudinal assessment. Virologic and immunologic variables tested on samples obtained prenatally and within 72 hours of delivery will be analyzed in a population of seropositive pregnant women and correlated with the infection outcome of their infants to evaluate maternal factors associated with transmission. The second population, the infants born to the seropositive mothers, will be tested sequentially from birth with a group of diagnostic assays to evaluate the utility of these assays in infants at risk for infection. The final population, infants originally identified in the first phase of the prospective study (1986 to 1991), provides a unique group in which to extend neurodevelopmental and other clinical and laboratory assessments to determine the long term outcome of infection and identify factors associated with progression of disease. These studies will expand our understanding of perinatal transmission and may provide data that will be useful in devising strategies for prevention and earlier detection of infection or disease.